There is no difference between vitamin D2 and D3 for raising blood levels of the vitamin, but D3 is superior for sustaining those levels, says a new study from Argentina.

Supplementation with large doses of vitamin D2 or D3 forms boosted blood levels of the vitamin (as measured by 25(OH)D levels), but declines in 25(OH)D were more rapid in the D2 group, compared with the D3 group, report scientists from the Hospital de Clinicas in Buenos Aires and the Universidad de Buenos in Buenos Aires

Fifty days after the last dose of vitamin D, the D2 group’s 25(OH)D levels were the same as those in the placebo group, but elevated levels were still observed in the D3 group, according to findings published in the European Journal of Clinical Nutrition​​.

“In the long term, vitamin D3 seems more appropriate to sustain adequate levels of 25OHD, which could be relevant for classic and non-classic effects of vitamin D,”​ wrote the researchers.

The sunshine vitamin​

According to the 2014 CRN Consumer Survey on Dietary Supplements, vitamin D is the second leading category among supplement users after multivitamins.

Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. Both D3 and D2 precursors are transformed in the liver and kidneys into 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D).

Vitamin D deficiency in adults is reported to precipitate or exacerbate osteopenia, osteoporosis, muscle weakness, fractures, common cancers, autoimmune diseases, infectious diseases and cardiovascular diseases. There is also some evidence that the vitamin may reduce the incidence of several types of cancer and type-1 and -2 diabetes.

While our bodies do manufacture vitamin D on exposure to sunshine, the levels in some northern countries are so weak during the winter months that our body makes no vitamin D at all, meaning that dietary supplements and fortified foods are seen by many as the best way to boost intakes of vitamin D.

D2 vs D3 ​

Several studies have reported that the D3 form of the vitamin is more potent that D2, with a study led by Robert Heaney, MD, from Creighton University in Nebraska reporting earlier this year that D3 was 87% more potent than D2 (Journal of Clinical Endocrinology & Metabolism​, doi: 10.1210/jc.2010-2230).

A 2012 analysis of data from seven randomized controlled trials published in the American Journal of Clinical Nutrition​​ indicated that the majority of the evidence supports the hypothesis that D3 is more effective than D2.

“A central point for framing the discussion about the best supplementation is the understanding about the continuous or discontinuous need of some level of vitamin D in blood,” ​explained the Buenos Aires-based scientists. “In addition to the well-known effect on bone, vitamin D possesses pleiotropic actions on the immune and endocrine systems, and on common cell functions, such as proliferation and differentiation. ​

“Most of these non-classic effects depend upon the tissue-specific regulation of 1,25(OH)2D, which requires adequate blood levels of 25OHD as substrate, suggesting that prolonged or continuous level of 25OHD could be worthwhile.”​

Study details​

Led by Beatriz Oliveri, the researchers recruited 33 healthy people with an average age of 33 and divided them into three groups: One group was placebo, and the other two received a starting dose of 100,000 IU of either vitamin D2 or D3. One week later they were then given 4,800 IU per day of the same D form for a further two weeks. The participants were monitored for a total of 11 weeks.

Results showed that the starting dose of D2 and D3 boosted 25OHD levels to similar levels. The area under the curve for 25(OH)D was 28.6% higher for D3 compared with D2 between day 7 and day 77, said the researchers.

“[A]fter a period with the same daily doses of vitamin D2 and D3, the 25OHD levels in the group that received vitamin D2 declined faster than the levels in the vitamin D3 group, reaching similar levels as the placebo group at the final point,” ​they wrote.

“A different AUC among vitamin D-supplemented subjects could be clinically relevant if adequate levels of 25OHD were continuously required. If this were the case, vitamin D3 use could be a better option. The rationale for a need of continuous 25OHD is currently insufficient, although some evidence suggests that such levels are worthwhile, in particular for non-classic vitamin D effects, which seem mediated via localized autocrine or paracrine synthesis of 1,25(OH)2D depending on the adequacy of 25OHD levels.”​